Diagnostic and Prognostic Performance of Liquid Biopsy-Derived Exosomal MicroRNAs in Thyroid Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC.

Circulating microRNAs and Clinicopathological Findings of Papillary Thyroid Cancer: A Systematic Review

“…To the best of our knowledge, this is the first systematic review that focuses on whole blood circulating miRNAs and the clinicopathologic features of PTC. A recently published meta-analysis included studies with other subtypes of differentiated thyroid cancer as well as focused on exosomal miRNAs, excluding studies that investigate the whole serum or plasma (64). Several miRNAs were identified to differentiate healthy controls or patients with benign thyroid nodules from PTC patients.…”

Promising developments in the fi eld of diff erential diagnosis of benign and malignant thyroid nodules

“…изучили диагностическое значение экзосомальных микроРНК в диагностике рака ЩЖ. Учёт содержания в плазме трех микроРНК (miR-146b-5p, miR-223-5p и miR-182-5p) позволял отличать злокачественные узлы с чувствительностью 93,8% и специфичностью 92,9%, также отмечено, что микроРНК могут иметь предиктивное значение для рака ЩЖ [36]. В настоящее время созданию эффективных способов определения злокачественности узлов ЩЖ посредством оценки циркулирующих ми-кроРНК препятствует отсутствие стандартизованных протоколов анализа [37].…”

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

“… 2 , 3 , 4 Accumulating evidence indicates that several protein‐coding and non‐coding genes play essential roles in TC development and progression. 2 , 5 , 6 , 7 , 8 …”

“…[2][3][4] Accumulating evidence indicates that several protein-coding and non-coding genes play essential roles in TC development and progression. 2,[5][6][7][8] Long non-coding RNAs (lncRNA), a group of endogenous cellular transcripts more than 200 nucleotides in length, have been involved in multiple pathophysiological processes of the human body, especially tumorigenesis and progression of cancers. 9 The aberrant expression of lncRNA processes crucial functions involved in proliferation, apoptosis, and metastasis through abnormal regulation of gene expression transcriptionally and post-transcriptionally.…”

“…Understanding the pathogenesis of TC and finding biomarkers for its early diagnosis and effective treatment are current focal points of research 2–4 . Accumulating evidence indicates that several protein‐coding and non‐coding genes play essential roles in TC development and progression 2,5–8 …”